Summary Because MYC plays a causal role in many human cancers, including those with hypoxic and nutrient-poor tumor microenvironments, we have determined the metabolic responses of a MYC-inducible human Burkitt lymphoma model P493 cell line to aerobic and hypoxic conditions, and to glucose deprivation, using Stable Isotope Resolved Metabolomics. Using [U-13C]-glucose as the tracer, both glucose consumption and lactate production were increased by MYC expression and hypoxia. Using [U-13C,15N]-glutamine as the tracer, glutamine import and metabolism through the TCA cycle persisted under hypoxia, and glutamine contributed significantly to citrate carbons. Under glucose deprivation, glutamine-derived fumarate, malate, and citrate were significantly increased. Their 13C labeling patterns demonstrate an alternative energy-generating glutaminolysis pathway involving a glucose-independent TCA cycle. The essential role of glutamine metabolism in cell survival and proliferation under hypoxia and glucose deficiency, makes them susceptible to the glutaminase inhibitor BPTES, and hence could be targeted for cancer therapy.
Otto Warburg observed a peculiar phenomenon in 1924, unknowingly laying the foundation for the field of cancer metabolism. While his contemporaries hypothesized that tumor cells derived the energy required for uncontrolled replication from proteolysis and lipolysis, Warburg instead found them to rapidly consume glucose, converting it to lactate [1]. The significance of this finding, later termed the Warburg effect, went unnoticed by the larger scientific community at that time. The field of cancer metabolism lay dormant for almost a century awaiting advances in molecular biology and genetics which would later open the doors to new cancer therapies.
Otto Warburg observed a peculiar phenomenon in 1924, unknowingly laying the foundation for the field of cancer metabolism. While his contemporaries hypothesized that tumor cells derived the energy required for uncontrolled replication from proteolysis and lipolysis, Warburg instead found them to rapidly consume glucose, converting it to lactate even in the presence of oxygen. The significance of this finding, later termed the Warburg effect, went unnoticed by the broader scientific community at that time. The field of cancer metabolism lay dormant for almost a century awaiting advances in molecular biology and genetics, which would later open the doors to new cancer therapies [2, 3].
Public discourse on the state of the environment has been frequent and substantive over the past few decades. International debates have brought forth fruitful solutions to emerging ecological and environmental problems. However, the concept of 'justice' still eludes concerted thought. As a concept which is rapidly gaining significance in the South, environmental justice (EJ) is all about incorporating environmental issues into the broader intellectual and institutional framework of human rights and democratic accountability and is essentially anthropocentric in nature. As a movement originating within the African-American community in the US, it has been rather slow in achieving the recognition it deserves in the context of environmental policy research. One reason for this is that the traditional or dominant development discourse has always tried to mask issues related to identity, like race, class, caste, sexuality, and gender (Kurien, 1996). This reluctance to accede to the social context feeds into the social constructions of identity which in turn are incorporated into institutional and systemic structures and ultimately inform environmental policy-making.
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